Small Intestinal Bacterial Overgrowth: Updates and Clinical Implications. Christine Stubbe, ND, FABNO

Transcription

1 Small Intestinal Bacterial Overgrowth: Updates and Clinical Implications Christine Stubbe, ND, FABNO

2 Lahnor Powell, ND, MPH Medical Education Specialist - Atlanta

3 Christine Stubbe, ND, FABNO

4 Technical Issues & Clinical Questions Please type any technical issue or clinical question into either the Chat or Questions boxes, making sure to send them to Organizer at any time during the webinar. We will be compiling your clinical questions and answering as many as we can the final 15 minutes of the webinar. DISCLAIMER: Please note that any and all s provided may be used for follow up correspondence and/or for further communication.

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6 Small Intestinal Bacterial Overgrowth: Updates and Clinical Implications Christine Stubbe, ND

7 Learning Objectives Overview of SIBO Learn when to consider testing for SIBO Review the test in detail Discuss treatment recommendations Case examples GI and other test considerations

8 What is Small Intestinal Bacterial Overgrowth? Small Intestinal Bacterial Overgrowth is a heterogeneous syndrome characterized by an increased number and/or abnormal type of bacteria in the small bowel. SIBO is a condition in which the small bowel is colonized by excessive numbers of aerobic and anaerobic microbes that are normally found in the large intestine. Currently a bacterial concentration of >10 3 c.f.u./ml is generally considered significant. Sachdev AH, et al. Therapeutic advances in chronic disease. Sep 2013;4(5): Rezaie A, et. al. The American Journal of Gastroenterology. 2017;112:

9 Bacterial Concentrations Throughout the GI Tract Mowat A, et al. Nature Review Immunology. 2014;14(10):

10 Ways the Body Innately Prevents the Overgrowth of Bacteria in the Small Intestine Gastric acid Pancreatic and biliary secretions Peristalsis and the migrating motor complex (MMC) stasis promotes bacterial growth Ileocecal valve prevents reflux of colonic bacteria into the small intestine The compromise of any of these processes can lead to the development of SIBO Bures J, et al. World Journal of Gastroenterology. 2010;16(24): Husebye E. Neurogastroenterology and Motility. 1999;11(3): Machado WM, et al. Arquivos de Gastroenterologia. 2008;45(3): Pyleris E, et al. Digestive Disease and Science. 2012;57(5): Williams C. Best Practice and Research. Clinical Gastroenterology. 2001;15(3):

11 When to Consider SIBO? Signs and Symptoms Associated Conditions and Risk Factors

12 What are the Common Signs and Symptoms of SIBO? Abdominal bloating Excessive gas or belching Abdominal cramps Diarrhea Constipation Nausea Heartburn Steatorrhea Nutrient deficiencies Vitamin B12 Iron Macronutrient malabsorption Fat-soluble vitamins RBC folate

13 Conditions with a High Prevalence of Overgrowth Functional GI and motility disorders (such as IBS & gastroparesis) Neuromuscular Diseases (such as restless leg syndrome) Inflammatory Bowel Disease (IBD) Pancreatic disease Celiac disease Hypothyroidism Liver disease Diabetes Fibromyalgia Rosacea Parkinson s disease Obesity Plus many other conditions Costa MB, et al. Arquivos de Gastroenterologia. 2012;49(4): Lauritano, et. al. Journal of Clinical Endocrinology and Metabolism. 2007;92(11): Martins CP, et al. Arquivos de Gastroenterologia. 2017;54(2): Quera PR, et al. Revista Medica de Chile. 2005;133(11):

14 Prevalence of SIBO in Common Conditions IBS 78% of patients positive 48% of patients treated successfully for SIBO no longer met Rome criteria Fibromyalgia and Chronic Fatigue Syndrome 42/42 patients with fibromyalgia had an abnormal lactulose breath test with significantly greater hydrogen production; significant correlation between degree of pain and peak hydrogen level 77% of CFS patients were found to have SIBO Hypothyroidism 54% of patients with hypothyroidism have SIBO compared with 5% of controls Hypo- and hyperthyroidism, often of autoimmune origin, are respectively associated to small intestinal bacterial overgrowth and to changes in microbiota composition. Lauritano EC, et. al. Journal of Clinical Endocrinology and Metabolism. 2007;92(11): Pimentel M, et.al. Annuals of the Rheumatic Diseases. 2004;63(4): Pimentel M, et al. American Journal of Gastroenterology. 2000;95(12): Pimentel M, et. al. American Journal of Gastroenterology. 2000;118(4):A414. Virili C, et al. Endocrine. 2015; 49(3):

15 What are Risk Factors for the Development of SIBO? Mechanical Stasis Structural/Anatomic: Small intestine diverticula, strictures, surgery Motility Disorders: Gastroparesis, Medications (i.e. opioid analgesics) Irritable Bowel Syndrome Hypothyroidism Metabolic Disorders: Diabetes Elderly Age Organ System Dysfunction: Liver, kidney, pancreatic dysfunction, Crohn s, Celiac Immunodeficiency states Hypochlorhydria Medications: Recurrent antibiotics and gastric acid suppressors GI Infection Dukowicz AC, et al. Gastroenterology and Hepatology. 2007;3(2): Martins CP, et al. Arquivos de Gastroenterologia. 2017;54(2):91-95.

16 SIBO Can Cause Histopathologic Change of Small Intestine An overgrowth of bacteria in the small intestine can cause: Blunting of the villi Thinning of the mucosa and crypts Increased intraepithelial lymphocytes Microscopic inflammatory changes Haboubi NY, Lee GS, Montgomery RD. Age Ageing. 1991;20: Bures J, et. al. World Journal of Gastroenterology. 2010;16(24): Lappinga, P, et. al. Arch Pathol Lab Med. 2010;134(2):

17 Testing for SIBO Gold Standard: Aspirate and Culture Breath Testing

18 Gold Standard Aspirate of small bowel fluid followed by culture and bacterial count Disadvantages Invasive procedure as the small intestine must be intubated so that aspirates can be collected Culture-based techniques do not allow for growth of all organisms, thus may underestimate the bacterial population Potential for contamination of instrumentation and inaccurate sampling due to technical problems Endoscopy can only reach the upper portion of the small intestine and colonoscopy can only reach the lower, thus the substantial middle section of the small intestine is not accessible by this method Dukowicz AC, et al. Gastroenterology and Hepatology. 2007;3(2):

19 Breath Testing versus Small Bowel Aspiration Unlike breath testing, small bowel aspiration is invasive, timeconsuming and costly. Breath Testing is a useful, inexpensive, simple and safe diagnostic test in the evaluation of common gastroenterology problems. Rezaie A, et. al. The American Journal of Gastroenterology. 2017;112:

20 Breath Testing for SIBO Baseline breath measurement Drink substrate (lactulose) Lactulose transits through small intestine - if bacteria are present, H2 (hydrogen) or CH4 (methane) gas is produced H2 and CH4 absorbed through intestines into bloodstream Gases carried to lungs through bloodstream and expired Breath collected at timed points Rana SV, et al. World Journal of Gastroenterology. 2014;20(24):

21 Testing Substances for SIBO Breath Test Lactulose Cannot be digested or absorbed by humans, thus passes through entire length of small intestine Advantage: Can diagnose distal overgrowth which is thought to be more common Not as sensitive as glucose Glucose Glucose is absorbed within first few feet of small intestine, thus can only diagnose proximal overgrowth Disadvantage: Cannot diagnose distal overgrowth Accurate diagnosis of proximal overgrowth

22 Collection Pack Instructions Very important to review the instructions with the patient as they are detailed and specific Improper collection can lead to ambiguous results Key instructions: 4 weeks prior: No antibiotics, colonoscopy or barium enema 7 days prior: No laxatives, stool softeners, stool bulking agents or antacids 24 hours prior: Diet limited to a few foods and no probiotics 12 hours prior (fasting with only water): No non-essential medications/supplements, toothpaste, gum, candies or mouthwash 1 hour prior and during testing (fasting with only water): No smoking, sleeping, vigorous exercise or toothpaste

23 Collection Pack Instructions Continued Collection technique with timing and breathing into the tube may need to be reviewed with the patient Breathe normally, inhale and hold 5 seconds Exhale normally into mouthpiece (do not blow hard) Insert tube and remove after 2 seconds Record times on labels and requisition form Great demonstration video for patients to watch can be found on the SIBO page on

24 Test Interpretation

25 2017 North American Breath Testing Consensus Guidelines Standardization was lacking regarding indications for testing, test methodology and interpretation of results Who formed the consensus group? Consensus was reached on 26 statements in the areas of indications, preparation, performance, interpretation of results and knowledge gaps Rezaie A, et. al. The American Journal of Gastroenterology. 2017;112:

26 Breath Tests: 3-Hour versus 2-Hour 3-Hour SIBO Breath Test 2-Hour SIBO Breath Test

27 Test Components Graph of hydrogen (H2) and methane (CH4) Chart of breath gases at the timed points Carbon dioxide (CO2) evaluation for quality control Actual collection times Evaluation for hydrogen Evaluation for methane

28 Evaluation for Hydrogen (H2) A rise of H2 of >20 ppm over baseline in the first 90 minutes of testing is positive for SIBO Genova s Evaluation for hydrogen based on consensus paper; this cut point is seen widely throughout the literature

29 Evaluation for Hydrogen Significance of elevated baseline H2 levels in patients reporting adherence to fasting and dietary guidelines is not known In a symptomatic patient, some clinical groups with expertise in SIBO management may consider an elevated hydrogen baseline a positive test Approximately 8 to 27% of individuals do not produce H2 due to the presence of methanogenic microbiota which consume hydrogen molecules to produce methane gas Low H2 findings through all time points in a symptomatic patient may reflect a false negative result Clinical attention should be shifted to evaluation of CH4

30 Evaluation for Methane (CH4) The consensus group and other papers refer to an absolute value of 10 or greater at any point during the test as a methane positive result Results 10+ will be outlined in red and flagged with an H Peer-reviewed literature suggests an association with certain clinical conditions and methanogen overgrowth at levels as low as 3 ppm, CH4 values between 3 and 9 may indicate the need for clinical intervention in the symptomatic patient Results 3-9 will be outlined in yellow Emerging literature suggests that unlike H2, an elevated CH4 level at baseline is common

31 Evaluation for Methane Utilization of breath methane levels for SIBO assessment is controversial largely due to a lack of validation related to diagnostic specifics such as timing and magnitude of increase The rise of CH4 during breath testing appears to not be as sharp as H2 However, CH4 measurements are increasingly obtained to address other clinical questions such as: Constipation Methane gas itself may slow intestinal transit, and patients with CH4-predominant bacterial overgrowth have been found to be five times more likely to have constipation compared to individuals with H2 predominant overgrowth The severity of constipation has been found to directly correlate with the CH4 level Irritable Bowel Syndrome (IBS) Obesity

32 Carbon Dioxide (CO2) Carbon Dioxide (CO2) is measured in every sample. CO2 levels exceeding acceptable limits indicate room air contamination likely at the time of sample collection. If CO2 levels exceed acceptable limits, sample integrity is questionable and results are designated as non-reportable (NR).

33 Actual Collection Times On the report On the requisition form

34 Actual Collection Times Actual Time The actual time of collection of samples is provided to enhance clinical interpretation The actual times reported are utilized to determine the actual interval for comparison to the recommended interval Actual Interval The actual interval can be compared to the recommended collection interval. If the recommended collection interval is not followed correctly, interpretation should be made within the context of the altered collection schedule. Generally, deviations of a few minutes will not significantly alter the interpretation. If the 90-minute interval is missed, evaluation for hydrogen may be affected, since the criteria for diagnosis of hydrogen-producing bacterial overgrowth is by 90-minutes

35 Treating SIBO Treat the overgrowth Provide nutritional support Correct the underlying cause

36 Treating SIBO For the majority of patients diagnosed with a positive breath test, SIBO will likely be a chronic and relapsing condition For example, one study found that 44% of patients treated successfully with antibiotics relapse within 9 months Goals of treatment are threefold: Treat the overgrowth Provide nutritional support Correct the underlying cause Dukowicz AC, et al. Gastroenterology and Hepatology. 2007;3(2): Lauritano EC, et al. The American Journal of Gastroenterology. 2008;103(8):

37 Treating SIBO Treat the Overgrowth Rifaximin Rifaximin plus Neomycin (or Metronidazole) Botanicals Berberine Allicin (component of garlic) Oregano oil Neem Others Chedid V, et al. Global Advances in Health and Medicine: Improving Healthcare Outcomes Worldwide. 2014;3(3):16-24.

38 Treating SIBO Provide Nutritional Support Nutritional consequences include: Weight loss Fat soluble vitamin deficiency Vitamin B12 deficiency Iron deficiency Low serum bile acids Low RBC folate levels Common diets prescribed for SIBO Specific Carbohydrate Diet (SCD) Low FODMAPs Elemental Diet

39 Treating SIBO Address the Cause The migrating motor complex (MMC) describes the waves of electromechanical activity that sweep through the intestines in a regular cycle The MMC is responsible for moving bacteria from the small intestine to the large intestine, as well as for inhibiting migration of colonic bacteria into the terminal ileum Supporting optimal function of the MMC includes: Meal spacing every 4-5 hours with overnight 12 hour fast Use of prokinetic agents Pharmaceutical agents such as low-dose erythromycin, Tegaserod, low-dose naltrexone, and Prucalopride Natural agents such as ginger, herbal bitters and the botanical product Iberogast Chaix A, et al. Cellular Metabolism. 2014;20(6): Vantrappen G, et al. The Journal of Clinical Investigation. 1977;59(6):

40 Treating SIBO Address the Cause Revisit the slide on risk factors and associated conditions. A few examples of addressing the cause may include: Discontinuation of medications: To be discussed between patient and clinician (acid-blocking medications, meds that slow transit- opioid analgesics, etc.) Treat Hypothyroidism Treatment with Levothyroxine associated with greater incidence of SIBO What is causing the hypothyroidism? Hypochlorhydria Bitters, Betaine HCl, etc. What is causing the hypochlorhydria? Some causes cannot be reversed (i.e. surgical alterations); ongoing management may be necessary. Consider visceral manipulation for adhesions is an informative website maintained by Dr. Allison Siebecker, ND, and includes treatment considerations Brechmann T, et al. World Journal of Gastroenterology. 2017;23(5):

41 Retesting In a patient treated for SIBO, many variables affect the decision of when to retest including the patient s underlying condition and its severity, length of treatment, etc The NA Consensus Group recommends that antibiotics should be avoided for 4 weeks prior to testing this recommendation usually applies to initial testing for SIBO However, there are emerging clinical recommendations which suggest retesting patients within a few days of antimicrobial course completion to ensure efficacy of the treatment. The North American Consensus group as well as others suggest that breath tests may be performed shortly after cessation of antibiotic therapy to confirm eradication Rezaie A, et. al. The American Journal of Gastroenterology. 2017;112:

42 Case Examples Case Example #1 Hydrogen positive, mild methane positive Case Example #2 Methane positive Additional Scenario

43 Case Example #1 34 yo female with bloating and alternating diarrhea with constipation Symptoms ongoing since she caught a GI bug while traveling in Central America 9 months ago; did not experience these symptoms previously Certain foods are problematic and she finds herself eating more paleo to try to control symptoms Patient is very active and keeps busy with work and travel; the IBS symptoms have interfered with daily living

44 Case Example #1 Hydrogen positive results Methane yellow moderate Collection schedule followed correctly

45 Case Example #1 Treatment: Since the patient did have a mixed IBS-type picture with alternating diarrhea and constipation, the clinician chose to treat both methane and hydrogen-producing bacteria Botanical regimen including Candibactin AR and BR plus Allimed (for methane) x 6 weeks Begin low FODMAPs diet Meal spacing every 4-5 hours Follow up: After 2 months, the patient symptoms had improved, so there was no follow up testing. The patient continued with the meal spacing and modified FODMAPs The goal is not continuous FODMAPs, since fermentable carbohydrate is important to the health of the commensal bacteria of the large intestine. The goal would be to introduce fermentable carbohydrates/resistant starches over time

46 Case Example #2 66 yo male with bloating and excessive belching and flatulence Severe constipation for as long as he can remember Has up to 2 bowel movements per week that are difficult to pass, he considers this pattern normal for him Obese, hypertension, hypothyroid, diabetic Takes oxycodone daily for a back injury 3 years ago Eats a standard American diet

47 Case Example #2 Methane-positive test Hydrogen normal Collection schedule followed correctly

48 Case Example #2 Treatment: The clinician chose to treat methane-producing organisms with Rifaximin plus Neomycin x 14 days A prokinetic was prescribed MotilPro (combination of ginger and 5HTP) indefinitely until chronic constipation resolves Magnesium was prescribed daily to assist with regularity Levothyroxine Rx was switched to Armour Thyroid Recommended increasing water intake from 1 cup daily to at least 1-2 L daily While fiber is important for constipation, it was avoided initially to address SIBO Low carbohydrate diet recommended (for diabetes, obesity, and SIBO)

49 Case Example #2 The long-term focus with this patient would be to work on his overall health conditions and habits that may predispose to SIBO (diabetes, hypothyroid, Standard American Diet, oxycodone use) The recurrence of SIBO is common especially if underlying conditions are not addressed This patient s lifestyle and health conditions are inflammation-promoting, so transitioning to anti-inflammatory diet/lifestyle may take time, in order to come off oxycodone A GI Effects Comprehensive stool analysis was also ordered for this patient If there are other GI abnormalities, for example pancreatic insufficiency, then pancreatic enzymes can be given to help with digestion (pancreatic insufficiency is common with diabetes)

50 Additional Scenario: Flatline Test Low H2 and CH4 throughout the test could indicate: It is a negative test for SIBO; consider other testing to assess etiology of patient symptoms If both H2 and CH4 are low all 3 hours, it may suggest the presence of H2S-producing bacteria The H2S-producing bacteria consume the H that would otherwise have gone to the bacteria that make H2 or CH4 H2S smells like rotten eggs, so if this is what the patient experiences, this may be the case The patient may not have followed collection pack instructions correctly The breath didn t make it into the tube They may have just completed antibiotics Instructions say wait 4 weeks after discontinuing antibiotics Some clinicians may advise their patient to collect immediately after finishing antibiotics to ensure efficacy of treatment Genova Diagnostics Banik GD, et al. Journal of Breath Research. 2016;10(2): Rezaie A, et al. The American Journal of Gastroenterology. 2017;112(5):

51 GI Test Considerations SIBO Other tests

52 Review: When to Order SIBO Testing IBS GI symptoms Bloating Intolerance to carbohydrates or FODMAPs Symptoms after eating Unexplained abdominal symptoms Predisposing conditions (see list) It is important to designate someone in the office to go over collection package instructions with each patient to ensure optimal results

53 Other GI Test Considerations for Similar Symptoms GI Effects is comprehensive and can identify: Pancreatic insufficiency Inflammation Dysbiosis Yeast overgrowth Parasitic infection Food Antibody panel Celiac and Gluten Sensitivity panel

54 GI Effects Comprehensive Profile GI Effects profile can not diagnose Small Intestinal Bacterial Overgrowth There are markers on this profile that can be suggestive of SIBO in the right patient population: Elevations in Products of Protein Breakdown Elevations in Fecal Fats Unexpected or extreme elevations in Total SCFAs and n-butyrate

55 Nutritional Insufficiencies B vitamins Macronutrients Fat-soluble vitamins The NutrEval assesses urine organic acids including malabsorption and dysbiosis biomarkers

56 Explore for more information and educational resources, including Lahnor Powell, ND, MPH Moderator Christine Stubbe, ND, FABNO Presenter LEARN GDX Brief video modules LIVE GDX Previous webinar recordings GI University Focused learning modules Conferences Schedule of events we attend Test Menu Detailed test profile information MY GDX Order materials and get results Questions?

57 Additional Questions? US Client Services: UK Client Services: Please schedule a complimentary appointment with one of our Medical Education Specialists for questions related to: Diagnostic profiles featured in this webinar How Genova s profiles might support patients in your clinical practice Review a profile that has already been completed on one of your patients We look forward to hearing from you!

58 Upcoming LIVE GDX Webinar Topics November 28, 2018 Stephen Goldman, DC Presents: The Rhythm Plus: Tracking a Full Cycle Through Salivary Hormone Testing Register for upcoming LIVE GDX Webinars online at The views and opinions expressed herein are solely those of the presenter and do not necessarily represent those of Genova Diagnostics. Thus, Genova Diagnostics does not accept liability for consequences of any actions taken on the basis of the information provided.

59 Small Intestinal Bacterial Overgrowth: Updates and Clinical Implications Christine Stubbe, ND, FABNO